1. Field of the Invention
The present invention provides conformationally dynamic peptides that are useful, for example, for detecting target proteins having a specific conformation, including misfolded proteins or proteins having a β-sheet secondary structure which may be associated with a disease. Also provided are methods of detecting such target proteins, diagnosing diseases associated with such target proteins or risk thereof, and treating diseases associated with such target proteins.
2. Background
The pathogenesis of misfolded protein disorders is characterized by the conversion of normal proteins into aggregation-prone β-sheet rich conformations. In the case of Alzheimer's disease (AD), self-assembly of amyloid beta (Aβ) protein into neurotoxic oligomers and fibrils is well supported as causative of disease. Other misfolded proteins associated with disease include prions in transmissible spongiform encephalopathy (TSE), cerebral amyloid angiopathy (CAA), and cerebral vascular disease (CVD); α-synuclein deposits in Lewy bodies of Parkinson's disease, tau in neurofibrillary tangles in frontal temporal dementia and Pick's disease; superoxide dismutase in amylotrophic lateral sclerosis; and Huntingtin in Huntington's disease. See, e.g., Glenner et al., J. Neurol. Sci. 94:1-28, 1989; Haan et al., Clin. Neurol. Neurosurg. 92(4):305-310, 1990.
U.S. Pat. No. 7,166,471, US 2006/0286672, US 2005/0026165, US 2008/0171341, US 2006/0057671 and US 2008/0095706 describe peptides useful for the detection of, for example, misfolded proteins, target protein having a predominantly β-sheet secondary structure, and target protein in a specific state of self-aggregation. The peptides described herein can be used in the methods described in any of these patent documents, the contents of each of which are incorporated herein by reference in their entirety.